The project consists of the following studies: 1) Determination of amino acid sequence of normal human G6PD and PGK, and determination of specific amino acid substitutions of variant enzymes. From these studies, molecular pathology of many G6PD and PGK variants associated with hemolytic anemia may be elucidated at the level of our present understanding of hemoglobin variants. Screening and characterization of new G6PD and PGK variants in various populations will be carried out. 2) Amino acid sequence of human embrionic hemoglobin chain (E-chain) will be determined. 3) Molecular abnormality of hexosaminidase, pseudocholinesterase, hypoxanthine guanine phosphoribosyl transferase and other enzymes related to genetic disorders will be studied. First, the normal enzymes will be purified to homogeneity and their chemical and biological properties will be studied. With this knowledge and with the use of a specific antibody, the molecular lesion of the variant enzymes from the patients will be studied. 4) Glycosyltransferases which synthesize specific blood group substances will be purified from plasma of various blood types, and biochemical and immunological properties of these transferases will be examined. From these studies, genetic mechanism of blood group determination will be elucidated. BIBLIOGRAPHIC REFERENCES: Yoshida, A., Lieberman, J. Gaidulis, L., and Ewing, C. "Molecular Abnormality of Human Alpha l-antitrypsin Variant (Pl-ZZ) Associated with Plasma Activity Deficiency. Proc. Natl. Acad. Sci., U.S.A. 73 1324-1328 (1976). Nagai, M., and Yoshida, A. "Isolation and Characterization of Blood Group Glycosyltransferases and Genetic Mechanism of Blood Group Determination." Fed. Proc. 35, 1441 (1976).